Improved survival in patients with FDG-PET/CT-based radiotherapy treatment planning for squamous cell anal cancer.

The aim of this retrospective analysis was to evaluate the impact of FDG-PET/CT-based target volume definition on locoregional control and survival, compared to conventional CT-based target volume definition and dose prescription. One hundred and twenty-two patients with squamous cell anal cancer were treated with curative radiotherapy (RT) alone (27%) or with RT with concurrent chemotherapy (73%) and analyzed. Forty-six percent had the early disease (stage I+II) and 54% were stage III. FDG-PET/CT-based staging was performed in 21% of the patients. The mean follow-up time was 60 months. Other risk factors affecting survival were investigated. According to initial staging in both groups (FDG-PET/CT and conventional CT) were 10% of stage IV disease, and they were excluded from radical radiotherapy and treated with palliative intent. Ninety-two percent of the patients achieved complete remission. Significant favorable factors in univariate analysis associated with disease-free survival (DFS) were PET/CT staging, T1/2 and N0 stage, and clinical stage I and II. Locoregional control (LRC) correlated with the T1/2 stage and initial performance status (PS) 0. There were no significant factors affecting overall survival (neither in univariate nor multivariate analysis). In multivariate analysis, the factor associated with better DFS was PET/CT staging and for LRC, PS 0 and concomitant chemoradiation. Acute toxicity was increased in the concurrent chemo-radiotherapy group. Two-, five- and ten-year overall survival rates were 83%, 69%, and 60%; disease-free survival rates were 76%, 73%, 73%; local control rates were 91%, 90%, and 90% and colostomy-free survival was 89%, 86%, and 81%, respectively. PET/CT staging allowed targeted dose escalation to the primary tumor and nodal metastases while decreasing dose to uninvolved regions, resulting in significantly improved DFS without compromising locoregional control.

Prospective evaluation of relationships between radiotherapy dose to masticatory apparatus and trismus.

AIMS: This feasibility study aimed to identify relationships between radiation doses to the masticatory apparatus as a combined block or as individual subunits with changes in trismus following radiotherapy. MATERIAL AND METHODS: Twenty patients from a single center were recruited prospectively as part of a randomized trial comparing proactive exercises in the management of trismus. Patients with stage III/IV oral cavity or oropharyngeal squamous cell cancers received intensity-modulated radiotherapy with concurrent systemic therapy. All patients had trismus prior to radiotherapy. Maximal inter-incisor distance (MID) was measured pre- and 6 months from the start of radiotherapy. Bilateral muscles of mastication: medial and lateral pterygoids (MP and LP), masseters (M), temporalis (T), temporomandibular joint (TMJ) were contoured on CT images. The block comprised all muscles excluding the TMJ below the orbital floor. Mean dose, equivalent uniform dose (EUD) and V35-V60 Gy were compared with change in MID. RESULTS: In six patients, the MID deteriorated at 6 months from the start of radiotherapy compared with 14 whose MID improved. No significant association was observed between age, gender, smoking, alcohol status, exercise compliance, cisplatin, tumor site, stage, V35-V60 Gy or EUD with change in MID. A clinical outlier was excluded. Without the outlier (n = 19), a significant association was seen between mean dose and change in MID at 6 months for the ipsilateral block (p = .01), LP (p = .04) and M (p < .01). All patients where trismus deteriorated at 6 months received mean doses >40 Gy to the block. CONCLUSION: Higher mean radiation doses to the ipsilateral block, LP and M were significantly associated with deterioration in trismus. Limiting dose to these structures to ≤40 Gy for tumors not invading the masticatory muscles may improve treatment-related sequelae. The ipsilateral block, LP and M should be studied further as possible alternative avoidance structures in radiotherapy treatment planning.

Association of Metformin Use and Survival Outcome in Women With Cervical Cancer.

OBJECTIVE: Although preclinical studies suggest possible antitumor effects of metformin against cervical cancer, there is currently a lack of clinical data examining the association of metformin use and survival in women with cervical cancer. The aim of this study was to examine survival of women with cervical cancer who were receiving metformin. METHODS: This is a retrospective study examining consecutive cases of stages I to IV cervical cancer between 2000 and 2014. Patient demographics, medication use, tumor characteristics, treatment patterns, and survival outcomes were correlated to metformin use. RESULTS: There were 70 (8.9%; 95% confidence interval [CI], 6.9-10.9) metformin users and 715 nonusers identified for the analysis. Median follow-up time was 22.6 months. Recurrence/progression of disease and death due to cervical cancer were observed in 236 and 163 cases, respectively. Metformin users were more likely to be older, hypertensive, diabetic, and dyslipidemic compared with nonusers (all, P < 0.05). On univariate analysis, metformin users and nonusers had similar progression-free survival (PFS) (5-year rates; 57.3% vs 61.8%; P = 0.82) and cervical cancer-specific overall survival (71.7% vs 70.7%; P = 0.86). After adjusting for patient demographics and tumor characteristics, metformin use was not associated with PFS (adjusted hazards ratio, 1.11; 95% CI, 0.70-1.74; P = 0.67) or cervical cancer-specific overall survival (adjusted hazards ratio, 0.91; 95% CI, 0.52-1.60; P = 0.75). Among 478 women who received whole pelvic radiotherapy, metformin use was not associated with PFS (P = 0.93) or cervical cancer-specific overall survival (P = 0.32). CONCLUSIONS: In this study population, metformin use was not associated with survival of women with cervical cancer.

Outcome of Radiation Monotherapy for High-risk Patients with Stage I Esophageal Cancer.

Currently, chemoradiation is the most widely used nonsurgical treatment for esophageal cancer. However, some patients, particularly the very elderly or those with severe vital organ dysfunction, face difficulty with the chemotherapy component. We therefore examined the outcome of radiation therapy (RT) alone for patients with esophageal cancer at our facility. Between January 2005 and December 2014, 84 patients underwent RT at our hospital, and 78 of these patients received concomitant chemotherapy. The remaining 6 patients underwent RT alone; these patients were considered to be high-risk and to have no lymph node metastasis (stage I). Five of them received irradiation up to a curative dose: 4 showed a complete response (CR) and 1 showed a partial response (PR). Of the patients exhibiting CR, 3 are currently living recurrence-free, whereas 1 patient underwent endoscopic submucosal dissection (ESD) as salvage therapy for local recurrence, with no subsequent recurrence. High-risk stage I esophageal cancer patients can be treated radically with RT alone under certain conditions. In the future, to broaden the indications for RT monotherapy to include some degree of advanced cancers, a novel concurrent therapy should be identified.

Expression of miR-296-5p as predictive marker for radiotherapy resistance in early-stage laryngeal carcinoma.

PURPOSE: Definitive radiation therapy is the mainstay of treatment for early stage laryngeal squamous cell carcinoma (LSCC). However, up to 30% of the patients do not respond to radiotherapy. Unfortunately, we are unable to predict which tumors are likely to respond to radiation, and which will be resistant and persist. Therefore, the development of novel markers to predict response to radiotherapy is urgently needed. This study was designed to evaluate the expression pattern of microRNAs (miRNAs) in LSCC in order to identify markers capable of segregating radioresistant and radiosensitive tumors and to investigate the relationship between the expression of these miRNAs and the prognosis of LSCC. METHODS: The expression profile of 667 miRNAs was determined in an initial screening of nine early-stage LSCC samples (5 radioresistant and 4 radiosensitive) using TaqMan Low-Density Array (TLDA). Real-time polymerase chain reactions were performed to validate the expression of selected miRNAs in an expanded LSCC cohort (20 radioresistant and 14 radiosensitive). The miRNA expression level was scored as high or low based on the median of the expression in the LSCC samples. RESULTS: A comprehensive miRNA expression profiling enabled the identification of four miRNAs (miR-296-5p miR-452, miR-183* and miR-200c) differentially expressed in radioresistant LSCC. Moreover, the analysis of additional 34 LSCC samples, confirmed the expression of miR-296-5p as significantly related to radioresistance (p = 0.002) as well as an association of this marker with recurrence (p = 0.025) in early stage laryngeal cancer. CONCLUSIONS: This study indicates that miR-296-5p expression is associated with resistance to radiotherapy and tumor recurrence in early stage LSCC, showing the feasibility of this marker as a novel prognostic factor for this malignance. Furthermore, miR-296-5p expression could be helpful in the identification of tumors resistant to radiotherapy; thus aiding the clinicians in the choice of the best therapeutic scheme to be used in each case.

Effects of docetaxel plus three-dimensional conformal radiation therapy on microvessel density and apoptosis expression in local advanced squamous non-small-cell lung cancer.

We examined the effects of weekly single-agent docetaxel plus three-dimensional conformal radiation therapy (3D-CRT) on apoptotic index (AI) and microvessel density (MVD) in local advanced non-small-cell lung squamous cancer patients and analyzed the correlation of MVD, AI, and 50% tumor shrinkage time (T0.5) The molecular mechanism of docetaxel radiosensitization was investigated. Sixty untreated patients with stage IIIA or IIIB lung squamous cancer were enrolled and randomly divided into two groups: observation (N = 30; 3D-CRT + docetaxel + adjuvant chemotherapy) and control (N = 30; 3D-CRT + adjuvant chemotherapy). From day 1 radiotherapy, the observation group received intravenous docetaxel (36 mg/m(2)) once weekly for 6 weeks. Post-radiotherapy, chemotherapy of docetaxel combined with cisplatin lasted 4-6 cycles in both groups. Before radiotherapy and within 24 h after radiotherapy (20 Gy), bronchoscopic biopsy was performed twice at the same site. To analyze the MVD of tumor specimens with immunohistochemical staining . The AI of lung cancer cells was assessed with TUNEL assay, T0.5 values were calculated. The observation group had significantly lower MVD than the control group (P < 0.05). AI significantly increased before and after treatment in the observation group compared with the control group (P < 0.05). The decreased MVD values negatively correlated with T0.5 values (r = -0.624, P < 0.05), whereas the increased AI values did not correlate with the T0.5 values. Docetaxel radiosensitization may occur by decrease in MVD and increase in AI values. Weekly single-agent docetaxel plus 3D-CRT can improve prognosis and quality of life in local advanced non-small-cell lung squamous cancer patients.

Sleep-related breathing disorders in patients with tumors in the head and neck region.

BACKGROUND: Sleep disturbance is a prominent complaint of cancer patients. Most studies have focused on insomnia and cancer-related fatigue. Obstructive sleep apnea (OSA) has been reported in small studies and case reports. METHODS: In a retrospective review of patients who underwent formal sleep evaluation and polysomnography (PSG) from 2006 to 2011, 56 patients with tumors in the head and neck region were identified. Clinical characteristics, sleep-related history, and PSG data were reviewed. RESULTS: Most patients had active cancer (80%), and the majority had squamous pathology (68%). Prominent symptoms included daytime fatigue (93%), daytime sleepiness (89%), and snoring (82%). Comorbid conditions primarily included hypertension (46%) and hypothyroidism (34%). Significant sleep-related breathing disorder was noted in 93% of patients, and 84% met clinical criteria for OSA. A male predominance (77%) was noted, and patients were not obese (body mass index <30 kg/m(2) in 52%). The majority of patients (79%) underwent radiation prior to sleep study, of which 88% had OSA, and in the group without prior radiation, 67% had OSA. Adherence to positive airway pressure (PAP) therapy was slightly better when compared with the general population. A subset of patients with persistent hypoxia despite advanced forms of PAP required tracheostomy. Multivariate analysis revealed that patients with active disease and radiation prior to PSG were more likely to have OSA. CONCLUSION: Sleep-related breathing disorder was common in patients with tumors in the head and neck region referred for evaluation of sleep disruption, and most met clinical criteria for OSA. Daytime fatigue and sleepiness were the most common complaints. OSA was prevalent in male patients, and most with OSA were not obese. Architectural distortion from the malignancy and/or treatment may predispose these patients to OSA by altering anatomic and neural factors. A heightened clinical suspicion for sleep-related breathing disorder and referral to a sleep specialist would be beneficial for patients with these complaints.

Evaluation of the in vivo genotoxic effects of gamma radiation on the peripheral blood leukocytes of head and neck cancer patients undergoing radiotherapy.

The present study aimed to evaluate the genotoxic effects of ionizing radiation on non-target cells of Head and Neck Squamous Cell Carcinoma (HNSCC) patients exposed to various cumulative doses of gamma rays during radiotherapy. The ten patients (P1-P10) were treated with cobalt 60 gamma radiation (External Beam Radiotherapy) for a period of five to six weeks with a daily fraction of 2Gy for 5 days each week. The genotoxic effects of radiation (single strand breaks - SSBs) in these patients were analyzed using the alkaline single cell gel electrophoresis (SCGE) technique, with the Olive Tail Moment (OTM) as the critical parameter. A sample of each patient's peripheral blood before starting with radiotherapy (pre-therapy) served as the control, and blood collected at weekly time intervals during the course of the radiotherapy served as treated (10, 20, 30, 40, 50 and 60Gy) samples. In vivo radiosensitivity of these patients, as indicated by SSB's after the cumulative radiation doses at the various times, was assessed using Student's t-test. Significant DNA damage relative to the individual patient's pre-therapy baseline data was observed in all patients. Inter-individual variation of the genotoxic effects was analyzed using two-way ANOVA. The correlation between doses for the means of smoker and non-smoker patients was calculated using the Pearson test. The results of this study may indicate the need to reduce the daily radiotherapy dose further to prevent genotoxic effects on non-target cells, thus improving safety. Furthermore, these results may indicate that the estimation of DNA damage following exposure to a gamma radiation, as measured by the comet assay in whole blood leukocytes, can be used to screen human populations for radiation-induced genetic damage at the molecular level.

Locally advanced head and neck squamous cell cancer: treatment choice based on risk factors and optimizing drug prescription.

Despite the policy changes to decrease tobacco consumption and therapeutic advances in this disease, squamous cell carcinomas arising from the head and neck (HNSCC) continue to represent a common neoplasm and a leading cause of cancer-related mortality in Europe and worldwide. although different approaches have been evaluated, no treatment has currently been shown to be superior to cisplatin (Platinol, Corden Pharma) based chemoradiation in locally advanced HNSCC. Based on retrospective subgroup analyses from multiple large clinical trials, human papillomavirus (HPV) status has been shown to be a validated prognostic factor in oropharyngeal tumors. Patients with HPV-related tumors, especially those who are non-smokers, have generally excellent outcome as their tumors are highly sensitive to both chemotherapy and radiation, whereas those with tobacco-related and HPV-negative tumors, who continue to represent substantial number of cases in Europe, have worse prognosis with tumors that are more resistant to treatment. The goal of treatment de-intensification in patients with favorable risk is to avoid long-term and late toxicity, but this must be achieved without compromise of treatment efficacy. For those with risk factors that portend a worse prognosis, the question remains whether addition to or modification of conventional treatment regimens would improve upon therapeutic index. Innovative clinical trial designs specifically tailored to these risk groups are urgently needed.

Induction chemotherapy in head and neck cancer patients followed by concomitant docetaxel-based radiochemotherapy.

Concurrent chemoradiotherapy has become the standard of care for patients with inoperable squamous cell head and neck carcinoma. More recently, induction chemotherapy has been adopted as an approach in the management of these patients. We report the results of a phase II trial associating induction chemotherapy and concomitant chemoradiotherapy in a series of patients with inoperable squamous cell head and neck cancer. Twenty-nine patients with advanced squamous cell carcinoma ineligible for surgery were enrolled. Induction chemotherapy with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 21 days was administered for two cycles. Radiotherapy followed the induction phase. During radiotherapy, docetaxel was administered weekly at the dose of 33 mg/m(2) . Primary end point of the study was feasibility of treatment. Six (18%) patients failed to conclude the treatment schedule. Although response rates in evaluable patients were very high (disease control rate >90%), toxicities were a matter of concern. The reported treatment schedule proved infeasible. However, some modifications in ancillary therapies aimed at exploiting its efficacy could make it practicable.

Phase I study of concurrent selective lymph node late course accelerated hyper-fractionated radiotherapy and pemetrexed, cisplatin for locally advanced esophageal squamous cell carcinoma.

The optimized concurrent chemoradiotherapy has not been established for patients with advanced esophageal squamous cell carcinoma (SCC). The aim of the present study was to evaluate the safety and efficacy of concurrent chemotherapy and selective lymph node (SLN) late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) for the patients with thoracic SCC. Twelve patients with T3-4N0-1M0-1a thoracic esophageal SCC were included. The total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks. The concurrent chemotherapy protocol was as following: cisplatin 10 mg/m(2) on days 1-5 and 22-26, pemetrexed in escalating doses, from the base level of 500 mg/m(2) once every 21 days. The primary objectives were to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLTs). Secondary end point included determination of preliminary radiographic response rates. As a result, three patients were enrolled in dose level 1 with pemetrexed 500 mg/m(2) and nine patients in dose level 0 with 400 mg/m(2) , respectively. At dose level 1, DLTs occurred in two of three patients. However, only two of nine patients in Level 0 developed DLTs. The complete response and partial response were observed in eight and four patients, respectively. Furthermore, no patient experienced cancer progression with a median follow-up of 9 months. In conclusion, the concurrent SLN LCAF IMRT and chemotherapy is feasible. The MTD of pemetrexed in this regimen was 500 mg/m(2) and RD was 400 mg/m(2) . Although toxicities were common, the protocol was safe, well tolerated, and achieved an encouraging outcome.

Generalized subcutaneous edema as a rare manifestation of dermatomyositis: clinical lesson from a rare feature.

Generalized subcutaneous edema is a very rare manifestation of inflammatory myopathies. A 61-year-old woman presented with classic signs and symptoms of dermatomyositis. She was also noted to have generalized edema that was so florid that an alternative diagnosis was considered. Her disease was resistant to corticosteroids, azathioprine, and mycophenolate mofetil. Intravenous administration of immunoglobulins was started because of marked worsening of her disease-muscle weakness, generalized anasarca, and involvement of her bulbar muscles. This led to dramatic resolution of her subcutaneous edema and significant improvement of her skin and muscle disease. As the initial screen for malignancy was negative, a positron emission tomography-computed tomography scan was requested, which interestingly showed a metabolically active cervical tumor. Anasarca is an unusual manifestation of dermatomyositis. In treatment-refractory cases, it seems reasonable to consider positron emission tomography scan in excluding underlying malignant disease.

Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck.

BACKGROUND: Panitumumab has the potential to improve the therapeutic ratio of concurrent chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: This phase I dose-finding study investigated escalating doses of paclitaxel (Taxol) given concurrently with panitumumab, carboplatin and intensity-modulated radiotherapy (IMRT) for stage III-IVB SCCHN. Untreated patients with oral cavity, oropharynx, larynx, hypopharynx or unknown primaries were eligible. Additional eligibility criteria included measurable disease, good performance status and no contraindication to therapy. Patients received weekly fixed doses of panitumumab and carboplatin plus escalating doses of paclitaxel with IMRT. RESULTS: Nineteen patients were enrolled on to two dose levels (DLs): weekly paclitaxel 15 mg/m(2) (n = 3) and 30 mg/m(2) (n = 16). One dose-limiting toxicity occurred in DL 2, which was declared the maximum tolerated dose. All patients experienced mucositis, primarily grade 3 or more. Oral pain, xerostomia, dysphagia, weight loss, dermatitis, nausea and acneiform rash were frequent. All patients had partial response according to RECIST, whereas the overall complete clinical response rate was 95%. At median follow-up of 21 months, 18 of 19 patients (95%) remained disease free. CONCLUSIONS: Panitumumab, carboplatin, paclitaxel and IMRT are well tolerated and appear highly active in the treatment of SCCHN. Further study of this regimen in SCCHN is warranted.

[Taxan induction chemotherapy and concomitant chemoradiotherapy with cisplatin in patients with locally advanced head and neck cancer--early results]. / Chemioterapia indukcyjna taksanami z jednoczesna radiochemioterapia z udzialem cisplatyny u chorych z miejscowo zaawansowanymi nowotworami glowy i szyi--wyniki wczesne.

UNLABELLED: The growing number of patients with head and neck cancer is a reason to search for new effective treatment strategies. Results of treatment for locally advanced squamous cell head and neck cancer with surgery and/or radiotherapy are still unsatisfactory. During last decade concomitant chemoradiotherapy became a new standard in this group of patients. The treatment method is charged of high toxicity and real therapeutic advantages are obtained by limited number of patients. Intensive clinical investigations on novel therapeutic strategies are in progress. One of them is the combination of induction chemotherapy with taxan (TPF) and concomitant chemoradiotherapy join with cisplatin. The aim of the study was to estimate the treatment tolerance and early term results with combination of induction chemotherapy with TPF and concomitant chemoradiotherapy join with cisplatin in patients with locally advanced, squamous cell carcinoma of head and neck. MATERIAL AND METHODS: Patients with locally advanced oropharyngeal and larynx cancer treated in the Institute of Oncology in Bialystok at the Department of Radiotherapy II from latter half of 2009 year were included in the study. The treatment protocol consisted of 3 courses of induction chemotherapy TPF (Taxotere 75 mg/m2, DDP 100 mg/m2, 5-Fluorouracyl 1000 mg/m2 every 3 weeks) and conventionally fractionated radiotherapy (Df=2 Gy, 5 x weekly) to total dose of 66-72 Gy and for neck cervical lymph nodes up to 60-66 Gy with concomitant of cisplatin 100 mg/m2 every 3 weeks. Early reactions were estimated according to EORTC/RTOG scales, and chemotherapy tolerance was evaluated according to the CTC scale. Twelve patients with homogenous criteria were included in the study. RESULTS: The treatment tolerance was acceptable. However several adverse reactions were present. The main adverse effect was the extensive mucosal reaction. Neutropenia and anemia were also observed in most of the patients. Some patients complained of diarrhea, vomiting and nausea in mild or moderate intensity which were persisted temporarily. CONCLUSIONS: Induction chemotherapy TPF and concomitant radiochemotherapy with cisplatin in patients with locally advanced head and neck cancer in III-IV clinical stages came out as the treatment of high efficacy.

Prognostic factors in oropharyngeal cancer--analysis of 627 cases receiving definitive radiotherapy.

INTRODUCTION: The aim of this retrospective analysis was to analyze the results of conventional radical radiotherapy in the treatment of oropharyngeal cancer and to identify pre-treatment and treatment-related prognostic factors for outcome. MATERIAL AND METHODS: The records of 627 patients with oropharyngeal cancer treated with radical radiotherapy with conventional techniques were analyzed. RESULTS: The median age was 56 years. History of tobacco abuse was present in 80.5%. Eighty six percent had stage III or IV disease. Radical radiotherapy alone was the treatment modality for 71.2% and concomitant or neoadjuvant chemotherapy was used in 28.8%. The 3-year local control (LC), loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS) was 49%, 40.6%, 38.9% and 36.1% respectively. The 3-year DFS rates were 80.3% for stage I, 65.8% for stage II, 46.1% for stage III and 25.2% for stage IV disease. Multivariate analysis was performed for prognostic factors. Prior history of tobacco abuse was an independent prognostic factor for both DFS and LRC. Karnofsky Performance Score (KPS) < 80, higher nodal stage, lower total radiotherapy dose (<66 Gy) in those receiving > 60 Gy, and overall treatment time > 50 days were other independent prognostic factors for inferior DFS and LRC. KPS < 80, higher T stage, higher nodal stage, RT dose < 66 Gy and longer overall treatment time (>50 days) were independent prognostic factors for poorer local control. CONCLUSIONS: Several patient-, disease- and treatment-related variables independently affect survival outcomes after radical radiotherapy for oropharyngeal cancer. Oropharyngeal cancers in those without a history of tobacco abuse may be biologically different and more amenable to cure with radiotherapy.

Prognostic significance of keratinization in squamous cell cancer of uterine cervix: a population based study.

PURPOSE: To determine the influence of keratinization on prognosis in squamous cell cancer (SCC) of the uterine cervix. METHODS: Patients with keratinized squamous cell carcinoma (KSCC) and non-keratinized squamous cell carcinoma (NKSCC) of the cervix were identified from the Limited Use SEER database from 1988 to 2004. A subgroup of patients who did not have radiation or surgery formed the basis to study the natural history of the disease. Data were analyzed using Pearson Chi-square, Student's T tests. Kaplan-Meier and Cox Regression Proportional Hazards survival analysis was conducted in SPSS and SEER-Stat software. RESULTS: The KSCC group had 3,102 and the NKSCC had 3,751 patients with mean age being 51 and 49 years, respectively (P = 0.001). In general, patients with KSCC were more likely to have advanced stage (FIGO III and IV) disease while patients with NKSCC were more likely to have poorly differentiated neoplasms (P < 0.001). The prevalence of lymph node metastasis remained similar in both histology types (P > 0.05). Overall, the 5-year survival in KSCC was 63.4% as compared to 65.3% in the NKSCC group (P = 0.04). Patients treated by surgery had no difference in survival; however, patients treated by radiation had a median survival in KSCC of 33 months (n = 928, 95% CI 27.7-38.3) as compared to 38 months (n = 1,140, 95% CI 32.1-43.8) in NKSCC (P = 0.03). A total of 165 KSCC and 147 NKSCC patients did not receive treatment. Within this subgroup, the median survival was 10 months (95% CI 5.93-14.07) as compared to 28 months (95% CI 17.9-38.0; P = 0.001) respectively for the two cohorts. In multivariate analysis stage, treatment status, nodal metastasis and keratinization were independent predictors of survival (P < 0.05). CONCLUSION: This is the largest study reporting on the prognostic importance of keratinization in SCC. KSCC may be less radiosensitive and associated with shorter overall survival. Also, in the natural history of the SCC, keratinization signifies striking reduction in survival.

Using leptospermum honey to manage wounds impaired by radiotherapy: a case series.

Radiation-induced tissue injury and wounds with radiation-impaired healing are traumatic for patients and challenging for their caregivers. Standardized management approaches do not exist. The effect of Leptospermum honey as a primary dressing for managing these wounds was assessed in four patients (age range 63 to 93 years) who had previously undergone radiotherapy that left them with fragile friable areas of damaged skin that did not respond to conventional treatment. Compromised areas involved the neck, cheek, groin/perineum, and chest. In patients 1 and 2, after topical application of honey via hydrofiber rope and nonadhesive foam, respectively, improvements in the size and condition of wound/periwound area and a reduction in pain were noted before death or loss to follow-up. After including honey in the treatment regimen of patients 3 and 4, complete healing was noted in 2.5 weeks (with honey and paraffin) and 6 weeks (with honey-soaked hydrofiber rope), respectively. No adverse events were reported. Honey as an adjunct to conventional wound/skin care post radiation therapy shows promise for less painful healing in these chronic wounds. Prospective, randomized, controlled clinical studies are needed to confirm these observations.